PHGDH p.Glu487=
c.1461G>A · rs1005068896 · VCV1142664
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Conditions
1
PHGDH deficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.6 | GERP -1.4, phastCons 0.93 |
| Overall | ||
| CADD | 7.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/60,014 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00149%
24/1,613,842 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 15,004 |
| European (non-Finnish) | 0.00161% | 62,098 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PHGDH
- Protein
- p.Glu487=
- Coding
- c.1461G>A
- MANE Select
- NM_006623
- dbSNP
- rs1005068896
- Type
- single nucleotide variant
- Location
- chr1:119743899 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.06 · 21 PDB
Similar variants
- PHGDH c.1078+1G>A Likely pathogenic ★★ same condition
- PHGDH c.138+1G>T Likely pathogenic ★★ same condition
- PHGDH c.139-2A>G Likely pathogenic ★★ same condition
- PHGDH c.290+2T>C Pathogenic/Likely pathogenic ★★ same condition
- PHGDH c.357-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHGDH c.412-1G>C Likely pathogenic ★★ same condition
- PHGDH c.643+1G>A Likely pathogenic ★★ same condition
- PHGDH p.Arg135Trp Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/phgdh-p-glu487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown